Field asymmetric waveform ion mobility spectrometry (FAIMS) is gaining broad acceptance as a post-ionization separation method coupled to mass spectrometry (MS), e.g., as reviewed by Guevremont (J. Chromatogr. A 2004, 1058, 3). Unlike conventional ion mobility spectrometry (IMS) based on the absolute ion mobilities (K), FAIMS separates ions by the difference between K in a particular gas at high and low electric fields (E). In practice, this takes place in the gap between a pair of electrodes carrying an asymmetric high-voltage waveform (the analytical gap). Ions are typically moved through the gap by gas flow. Alternatively, in the longitudinal field-driven FAIMS described by Miller et al. (U.S. Pat. No. 6,512,224, U.S. Pat. No. 6,815,669), ions are moved by a weak electric field along the gap, created by segmented FAIMS electrodes or separate electrodes in addition to FAIMS electrodes. The asymmetric waveform (with peak amplitude known as dispersion voltage, DV) comprises a dc offset known as the compensation voltage (CV). At any CV value, only a small subset of ions with similar forms of K(E) may pass FAIMS, while other ions entering the gap become unbalanced and are eliminated by neutralization on either electrode. Thus the spectrum of an ionic mixture may be revealed by scanning or stepping CV over a relevant range. Application methods exploiting FAIMS have emerged in diverse areas, including proteomics, metabolomics, environmental and industrial quality control, natural resource management, and homeland security. To increase the separation peak capacity and specificity, FAIMS is typically coupled to other analytical stages downstream—MS and, more recently, conventional IMS and IMS/MS, e.g., as discussed by Tang et al. (Anal. Chem. 2005, 77, 6381).
The analytical gap of FAIMS devices may have a planar (p-) or curved (c-) geometry (in practice, a cylindrical, a spherical, or a sequential combination of cylindrical and spherical elements). The electric field is spatially homogeneous in planar but not in curved gaps. A time-dependent inhomogeneous field in a gap focuses ions to the gap median (or defocuses them away from the median), e.g., as discussed by Guevremont and Purves (Rev. Sci. Instrum. 1999, 70, 1370). The ion focusing in c-FAIMS and its absence in p-FAIMS have profound consequences for merits of those configurations, as described below.
A p-FAIMS has four intrinsic advantages over any c-FAIMS. In (1), ion focusing broadens the CV range of ions that achieve equilibrium within the gap and thus pass FAIMS regardless of the residence time. Hence p-FAIMS has a narrower CV pass band than a c-FAIMS, meaning an improved resolution, peak capacity, and specificity that allow one to separate (identify) species that cannot be distinguished or assigned using c-FAIMS. In (2), according to theoretical modeling of the present inventors, the resolution improvement is retained even at constant ion transmission efficiency, i.e., p-FAIMS provides not merely a higher resolution than c-FAIMS, but also a superior resolution/sensitivity balance (i.e., a higher resolution at equal sensitivity or higher sensitivity at equal resolution). In (3), ion focusing in c-FAIMS is not uniform: some ions (in general those with steep K(E) and thus high absolute CV) are confined more effectively than others, e.g., as discussed by Krylov (Int. J. Mass Spectrom. 2003, 225, 39). This greatly distorts the relative abundances of different ions in a mixture, which complicates quantification. In extreme cases, some ions (typically those with a virtually flat K(E) and thus near-zero CV) may be focused only marginally if at all, precluding their observation altogether. Absence of ion focusing in p-FAIMS means analyses without discrimination, with measured abundances closely reflecting the composition of sampled ion mixture. In (4), a c-FAIMS cannot process all ions simultaneously because the waveform of either polarity focuses some species but defocuses and eliminates others from the gap. For example, ions with positive K(E) slope (termed A-type) require one polarity (e.g., modes P1 or N1), while those with negative K(E) slope (C-type) require the opposite polarity (e.g., modes P2 or N2). The ion type depends on the carrier gas identity, temperature, and pressure: an ion may fall under different types under different conditions. In general, the ion type cannot be deduced a priori, and mixtures may comprise ions of more than one type. So analyses using c-FAIMS must often be repeated in both modes, reducing the duty cycle with a proportional impact on sensitivity. Planar FAIMS analyzes all ions in a single mode, with a significantly higher duty cycle.
The other two advantages of p-FAIMS are of a mechanical rather than a fundamental nature. In (5), unlike for c-FAIMS, the width of a planar gap may be adjusted easily and rapidly (e.g., for resolution control as reported by Shvartsburg et al., J. Am. Soc. Mass Spectrom. 2005, 16, 2). In (6), p-FAIMS allows a simpler, more compact design than curved geometries, which reduces the overall instrument size, weight, cost, and electrical power consumption.
Despite many benefits of p-FAIMS summarized above, practical FAIMS/MS systems have mostly adopted curved geometries: the cylindrical (taught, e.g., by Carnahan and Tarassov in U.S. Pat. No. 5,420,424) or “dome” (a cylinder with hemispherical terminus, taught, e.g., by Guevremont and Purves in WO 00/08455). That was mainly for the lack of effective MS interfaces for p-FAIMS. Ions in a planar gap are free to diffuse parallel to the electrodes (transversely to the gas flow), creating ribbon-shaped ion beams at the FAIMS exit. However, all inlets known in the art of MS and IMS have circular orifices. In systems involving atmospheric-pressure ionization (API) sources such as electrospray ionization (ESI) or atmospheric-pressure matrix assisted laser desorption ionization (AP-MALDI), the vacuum constraints of a 1st MS stage restrict the diameters of conductance limit apertures. Typical values (for either “heated capillary” or “curtain gas” interfaces) are ˜0.2-0.5 mm, as shown in FIG. 1. In comparison, a planar FAIMS gap normally spans ˜10-20 mm at least, producing ion beams with span of ˜5-10 mm and greater. Therefore, coupling p-FAIMS to standard MS (or low-pressure IMS) inlets results in huge ion losses. In contrast, a “dome” FAIMS could be readily interfaced to circular MS inlets with minimum ion losses.
In some FAIMS/MS systems, a cylindrical FAIMS is configured in a “side-to-side” (“perpendicular-gas-flow”) arrangement, as described, e.g., by Guevremont et al. (WO 01/69216), rather than in axial or dome geometry. Further variations of “side-to-side” FAIMS are described, e.g., by Guevremont et al.: a segmented device (WO 03/067236; US Pat. App. #20050151072) and an analyzer with a non-uniform gap width (WO 03/067243). In “side-to-side” FAIMS, the gas flow carries ions through the annular gap between two cylinders with coincident or parallel axes transversely, with ions exiting through a round hole on the opposite side of external cylinder. While ions in “side-to-side” FAIMS are focused to the gap median as in any c-FAIMS, they are free to diffuse parallel to electrode axis, also forming a ribbon-shaped beam in the FAIMS gap away from the injection point. This could result in significant ion losses when ions are extracted through a round exit orifice.
The above discussion with respect to planar vs. curved FAIMS geometries equally applies to higher-order differential ion mobility separation (HODIMS) analyzers as described, e.g., by Shvartsburg et al. (U.S. patent application, Ser. No. 11/237,523). In HODIMS, ions are separated based on the 2nd or higher K(E) derivatives (as opposed to the 1st derivative in FAIMS) using different asymmetric waveforms. Though HODIMS is not at all a part of FAIMS art, HODIMS analyzers may mechanically resemble those employed for FAIMS, with planar and “side-to-side” geometries equally possible for HODIMS. Hence the issues involved in coupling planar or “side-to-side” HODIMS devices to downstream stages would mirror those arising for FAIMS. Accordingly, any mention of FAIMS below will be understood to also cover HODIMS.
Ion mobility spectrometry with alignment of dipole direction (IMS-ADD) described by Shvartsburg et al. (US patent application Ser. No. 11/097,855) is a technology for separation and characterization of ions based largely on direction-specific ion-molecule cross sections, as opposed to orientationally-averaged cross-sections in conventional IMS. Though IMS-ADD is by no means a part of FAIMS art, IMS-ADD analyzers may mechanically resemble those employed for FAIMS and particularly for longitudinal field-driven FAIMS in a planar geometry. Hence the issues involved in coupling IMS-ADD devices to downstream stages would mirror those arising for p-FAIMS. Accordingly, any mention of FAIMS below will be understood to also cover IMS-ADD.
Fully exploiting the advantages of p-FAIMS or “side-to-side” FAIMS in FAIMS/MS, FAIMS/IMS, or FAIMS/IMS/MS systems is predicated on a practical interface between those FAIMS arrangements and the following stage. Accordingly, there is a need for new interfaces that could effectively capture ribbon-like ion beams and transmit them to downstream stages such as MS or IMS. The same challenge will arise whenever a rectangular or other non-circular ion beam is transmitted to MS, IMS, or another stage operating at a different (typically, but not necessarily lower) pressure. For example, such a non-circular beam may be generated by an ESI or AP-MALDI ion source comprising several emitters disposed along a line or in another non-circular arrangement.